12.14:
Acetals and Thioacetals as Protecting Groups for Aldehydes and Ketones
Acetals can selectively protect aldehydes and ketones against different reaction conditions. They are inert towards bases, oxidizing and reducing agents, and nucleophiles.
Since the aldehyde more rapidly transforms to an acetal than the ketone, in a compound containing both these groups, if reduction of the ketone is desired, the more reactive aldehyde is first selectively masked, and then the ketone is reduced.
After that, the aldehyde can be deprotected under mildly acidic conditions to obtain the selectively reduced product.
Analogously, thioacetal protection and deprotection can also be explored for selective reduction of functional groups.
Thioacetals are similar to acetals, except they are also stable under acidic conditions and can protect the carbonyl group in acidic and basic environments.
Mechanistically, thioacetals follow the same three steps: selective protection, desired reduction, and finally, deprotection.
In contrast to an acetal, which is hydrolyzed under mildly acidic conditions, a thioacetal, being inert to acids, is removed in the presence of mercuric chloride in aqueous acetonitrile.
12.14:
Acetals and Thioacetals as Protecting Groups for Aldehydes and Ketones
Acetals are formed by reacting two equivalents of alcohol with carbonyl compounds like aldehydes or ketones. Acetals are unaffected by bases, nucleophiles, oxidizing agents, and reducing agents. They serve as protecting groups for aldehydes and ketones. Acetals can be easily formed and also easily removed via mild acid hydrolysis.
In the presence of multiple functional groups, when selective reduction of one group over the other is desired, groups like aldehydes and ketones that form acetals readily can be protected from undergoing undesirable reactions. For instance, if a compound contains a ketone and an ester group, the ketone can be protected by converting it into acetal. On the other hand, the ester does not form acetal; hence it can be subjected to the desired reaction, and in the end, the ketone can be deprotected.
The sulfur-containing analogs of acetals are called thioacetals that can act as an efficient protecting group for aldehydes and ketones. The thioacetals are stable in acidic conditions. Due to this, they cannot be deprotected by acid hydrolysis. Instead, mercuric chloride in aqueous acetonitrile is used for its deprotection.
Apart from acting as protecting groups, thioacetals also play a major role in organic synthesis, especially in reduction reactions. Thioacetals can undergo desulfurization in the presence of Raney nickel and hydrogen to form hydrocarbons.
